ABSTRACT Pancreatic cancer is a disease with no effective treatment. It?s low five-year survival rate, estimated at between 6% and 7.7%, ranks it the fourth highest of cancer-related of death in the U.S. despite being the twelfth most common type of cancer. Each year in the U.S., there are nearly 50,000 new cases and more than 40,000 deaths caused by the disease. By 2030, pancreatic cancer is expected to be the second most common cancer-related cause of death in the U.S. Resistance of pancreatic cancer to current treatment regimens (both surgery and chemotherapy) contributes to the dismal prognosis of this malignancy. The current standard of care for pancreatic cancer is chemotherapy, namely gemcitabine, Abraxane and the Folfirinox regimens. Less than 25% of patients respond after enduring treatment 3.4 months of treatment costing $118,000. The price is high given the poor outcome: Disease progression is delayed an average of 5.5 months and death by 8.5 months. During the past decade, more than 20 phase II/III clinical trials sought out cures for pancreatic cancer, and none was successful. Today?s most effective regimens carry significant toxicities and offer marginal durable efficacy. Thus, there is a clear and unmet need for significant improvements in pancreatic cancer therapy. To this end, Avenzoar has developed a novel new chemical entity, AP-001, that interacts simultaneously with two proteins that are highly activated in pancreatic adenocarcinoma (PDAC): Glycogen synthase kinase 3 beta (GSK-3?) and histone deacetylase (HDAC). This Phase I project will establish dosage levels of AP-001 for animal studies, and then test the combination of AP-001 with standard treatments in a mouse model of pancreatic adenocarcinoma (PDAC) to determine relative efficacy as a key step to inform clinical trial design.